Abstract

Probiotics such as L. plantarum WCFS1 can modulate immune responses in healthy subjects but how this occurs is still largely unknown. Immune-sampling in the Peyer Patches has been suggested to be one of the mechanisms. Here we studied the systemic and intestinal immune effects in combination with a trafficking study through the intestine of a well-established immunomodulating probiotic, i.e. L. plantarum WCFS1. We demonstrate that not more than 2–3 bacteria were sampled and in many animals not any bacterium could be found in the PP. Despite this, L. plantarum was associated with a strong increase in infiltration of regulatory CD103+ DCs and generation of regulatory T cells in the spleen. Also, a reduced splenic T helper cell cytokine response was observed after ex vivo restimulation. L. plantarum enhanced Treg cells and attenuated the T helper 2 response in healthy mice. We demonstrate that, in healthy mice, immune sampling is a rare phenomenon and not required for immunomodulation. Also in absence of any sampling immune activation was found illustrating that host-microbe interaction on the Peyer Patches was enough to induce immunomodulation of DCs and T-cells.

Highlights

  • Probiotics are live microorganisms which, when administered in adequate amounts, confer health benefits on the host[1], such as enhanced clearance of pathogens, promoting intestinal epithelial survival and enhancing barrier function[2]

  • We investigated the systemic and intestinal immune effect in combination with a trafficking study through the intestine of a well-established probiotic strain, L. plantarum WCFS1, labeled with the luciferase from Pyrophorus plagiophthalamus emitting in the red spectra

  • Many studies demonstrate beneficial immune responses induced by probiotics, a key question that still needs to be addressed is how they interact with the gut immune system[23,24]

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Summary

Introduction

Probiotics are live microorganisms which, when administered in adequate amounts, confer health benefits on the host[1], such as enhanced clearance of pathogens, promoting intestinal epithelial survival and enhancing barrier function[2]. It is hypothesized that probiotics may modulate the immune system through two different pathways: (i) probiotics might be sampled by M cells in the Peyer’s patches (PPs) follicle-associated epithelium and modulate macrophages and dendritic cells (DCs) beneath the epithelium[5] or (ii) specific intestinal DCs in the mucosal lamina propria or PP sense intraluminal probiotics by pattern-recognition receptors (PRRs) on their dendrites[6,7] This contact with DCs, via either of both pathways, may regulate the maturation of antigen-presenting cells (APCs), and subsequently influence interactions with other effectors of the immune system, polarizing the subsequent antigen-specific T cell response towards Th1, Th2, Th17 or T regulatory cells[8]. We studied the effect of these bacteria on the systemic adaptive immune system after 5 days of oral administration, i.e. the period required to develop a T cell response in mice[17,18]

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